基于氧化应激反应探讨慢性体表溃疡发病机理及象皮生肌膏联合托里消毒散的干预作用

Pathogenesis of Chronic Body Surface Ulcers Based on Oxidative Stress Responses and Intervention Effect of Traditional Chinese Medicine

目的 探讨慢性体表溃疡发病机理以及象皮生肌膏联合托里消毒散的干预作用。方法 将30只SPF级雄性SD大鼠按随机数字表法分为空白对照组、模型组、象皮生肌膏组、托里消毒散组、象皮生肌膏联合托里消毒散组,每组各6只。采用金黄色葡萄球菌造模,连续给药1周后,检测创面组织中血管内皮生长因子(Vascular endothelial growth factor,VEGF)、血管内皮细胞生长因子受体2(Vascular endothelial growth factor receptor 2,VEGFR-2)、核因子E2相关因子2(Nuclear factor erythroid 2-related factor 2,Nrf2)、NAD(P)H醌氧化还原酶1[NAD(P)H quinone oxidoreductase1,NQO1)、血红素加氧酶1(Heme oxygenase-1,HO-1)]表达水平。结果 与空白对照组比较,模型组创面组织中VEGF、VEGFR-2表达均明显降低,差异有统计学意义(P<0.01);与模型组比较,象皮生肌膏组、托里消毒散组、象皮生肌膏联合托里消毒散组VEGF、VEGFR-2表达均明显升高,差异有统计学意义(P<0.01)。与对照组比较,模型组中Nrf2、NQO1、HO-1表达水平升高,差异有统计学意义(P<0.01);与模型组比较,象皮生肌膏组、托里消毒散组、象皮生肌膏联合托里消毒散组Nrf2表达水平均明显升高,NQO1和HO-1表达降低,差异有统计学意义(P<0.01)。结论 大鼠慢性溃疡的形成可能与氧化应激反应抑制了VEGF通路及Nrf2通路有关,而象皮生肌膏联合托里消毒散可能通过调节上述通路促进溃疡处血管新生和抗氧化应激,进而提高创面愈合能力。

Objective To explore the pathogenesis of chronic body surface ulcers and the intervention effect of Xiangpi Shengji Ointment combined with Tuoli Xiaodu Powder.Methods A total of 30 SPF-level male SD rats were randomly divided into the blank control group,model group,Xiangpi Shengji Ointment group,Tuoli Xiaodu Powder group,and Xiangpi Shengji Ointment combined with Tuoli Xiaodu Powder group,with six rats in each group.The model was made with Staphylococcus aureus.After one week of continuous administration,the expression levels of vascular endothelial growth factor(VEGF),vascular endothelial growth factor receptor 2(VEGFR-2),nuclear factor erythroid 2-related factor 2(Nrf2),NAD(P)H quinone oxidoreductase1(NQO1),and heme oxygenase 1(HO-1)in wound tissue were detected.Results Compared with the blank control group,the expression of VEGF and VEGFR-2 in the wound tissue of the model group decreased significantly,and the difference was statistically significant(P<0.01).Compared with the model group,the expression of VEGF and VEGFR-2 in the Xiangpi Shengji Ointment group,Tuoli Xiaodu Powder group,and Xiangpi Shengji Ointment combined with Tuoli Xiaodu Powder group were increased significantly(P<0.01).Compared with the blank control group,the expression levels of Nrf2,NQO1,and HO-1 in the model group increased(P<0.01).Compared with the model group,the expression level of Nrf2 in the Xiangpi Shengji Ointment group,Tuoli Xiaodu Powder group,and Xiangpi Shengji Ointment combined with Tuoli Xiaodu Powder group increased significantly,while the expression of NQO1 and HO-1 decreased(P<0.01).Conclusion The formation of chronic body surface ulcers in rats may be related to the inhibition of the VEGF pathway and Nrf2 pathway by oxidative stress responses,and Xiangpi Shengji Ointment combined with Tuoli Xiaodu Powder may promote angiogenesis and anti-oxidation stress in the skin ulcer of rats by regulating the above-mentioned pathways,so as to improve the healing ability of the wounds.